Proteins such as those intended for pharmaceutical applications can be manufactured using either a batch, fed batch method or a perfusion method. The present invention is directed to perfusion processes, including those used for manufacture of therapeutic proteins.
Perfusion processes for manufacturing therapeutic proteins are sensitive to changes in the composition of culture media, temperature, accumulation of metabolic wastes, and bioreactor physico-chemical parameters. Inadequate or fluctuating conditions affect protein posttranslational modifications such as its glycoprofile, the latter being known to correlate with pharmacokinetic properties.
Perfusion processing is desirable over fed-bath processing because it enables production of more product in a given period of time with improved cost of goods. Hence it is desirable to overcome the challenges of developing suitable feed conditions that will support a perfusion process.
U.S. Pat. No. 7,300,773 and EP 1,781,802 disclose production of the fusion protein TNFR-IG using a fed batch process in which feed media are prescribed having specified concentrations of amino acids and/or inorganic ions.